CEA is one of the best characterized tumor-associated antigens. Effective imaging of CEA- expressing tumors has been demonstrated in animals and human patients. Presently, all the CEA-binding antibodies approved for clinical use are murine in origin. The HAMA response seriously limits the applicability of these antibodies for therapeutic uses. Antibody T84.66 is the best anti- CEA antibody known but has an amino-acid sequence that does not correspond well to any known human framework. Thus, humanizing by transfer of CDRs is unlikely to provide an antibody of suitable affinity. Phage display allows efficient screening of libraries of human antibodies that contain between 10(8) and 10(10) members. CEA is a member of the Ig superfamily and many antibodies that bind CEA also bind other members of the family. City of Hope has produced a recombinant protein that contains a domain particular to CEA, "H6NA3." Using H6NA3 and CEA as targets, they propose to screen both FAB and single-chain Fv human antibody libraries to find binders. Many isolates will first be characterized while displayed on phage. The best candidates will be produced in E.coli and tested for affinity on BIAcore and for specificity by immunohistochemistry. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE